Ocular Biometric Characteristics in Preoperative Diagnosis of Acute Angle Closure Secondary to Zonular Laxity

doi:10.21203/rs.3.rs-2436011/v1

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Ocular Biometric Characteristics in Preoperative Diagnosis of Acute Angle Closure Secondary to Zonular Laxity

https://doi.org/10.21203/rs.3.rs-2436011/v1

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Purpose

To investigate the ocular biometric characteristics of eyes with acute angle closure (AAC) secondary to zonular laxity to further explore the sensitive parameters for preoperative diagnosis.

Methods

This study included 50 patients with AAC secondary to zonular laxity and 54 patients with acute primary angle closure (APAC). Demographic data, ocular examination results and biometric parameters on ultrasound biomicroscopy (UBM) images were compared between the affected and fellow eyes in two groups. Parameters significant in the multiple linear regression model were included in a regression equation and the diagnostic efficiency was evaluated by area under the curve (AUC).

Results

In patients with AAC secondary to zonular laxity, the binocular difference of central anterior chamber depth (ACD), lens vault (LV) in affected eyes and binocular difference of LV were significantly larger than those in patients with APAC respectively and these three parameters were all significant in multiple linear regression analysis (all P < 0.001). The AUC of binocular difference of ACD, LV in affected eyes and binocular difference of LV were 0.972, 0.796, and 0.855, respectively, with the cut-off value of 0.23 mm, 1.28 mm and 0.19 mm, respectively. The regression equation containing these three parameters was: ln (p/(1-p)) = -4.322 + 1.222[LV in affected eyes (mm)] + 3.657[binocular difference of LV (mm)] + 6.542[binocular difference of ACD (mm)], with the accuracy of prediction reaching 94.05%.

Conclusion

Binocular difference of ACD, LV in affected eyes, and binocular difference of LV had high efficiency in diagnosing AAC secondary to zonular laxity.

Health sciences/Medical research/Biomarkers/Predictive markers

Health sciences/Diseases/Eye diseases/Ocular hypertension/Glaucoma

Health sciences/Signs and symptoms/Eye manifestations

acute angle closure

zonular laxity

biometric characteristics

diagnosis

What was known before

Acute angle closure (AAC) is an ophthalmologic emergency that can lead to vision loss in a very short time. A challenge in treating AAC is to differentiate between patients with acute primary angle closure (APAC) and AAC secondary to zonular laxity.
Less hyperopic spherical equivalent, longer axial length, shallower anterior chamber depth, and higher lens vault increased the likelihood of zonular instability among patients with a history of AAC attack.

What This Study Adds

Binocular difference of ACD, LV in affected eyes with AAC, and binocular difference of LV had high efficiency in differentiating APAC and AAC secondary to zonular laxity.
The regression equation containing these three parameters could increase the accuracy in the preoperative diagnosis of AAC secondary to zonular laxity.

Acute angle closure (AAC) is an ophthalmologic emergency that can lead to vision loss in a very short time [1]. A challenge in treating AAC is to differentiate between patients with acute primary angle closure (APAC) and AAC secondary to zonular laxity [2], because patients with AAC secondary to zonular laxity could have similar symptoms and clinical features with APAC patients [3]. Previous researches [4, 5] have proved that zonular laxity is best assessed in phacoemulsification, finding the movement of the entire capsular bag during propagation of the capsular flap and anterior capsule striae during continuous curvilinear capsulorhexis (CCC). These signs could reflect the instability of the zonule, and if zonular dehiscence is not observed after full dilation of the pupil intraoperatively, zonular laxity could be diagnosed [6, 7]. However, there are no specific diagnostic criteria for determining zonular laxity in eyes with AAC before surgery.

In AAC cases with zonular laxity, the occurrence rate of complications during cataract surgery increases, with a risk of posterior capsule rupture, nucleus drop, intraocular lens (IOL) dislocation and so on [8]. If trabeculectomy is operated on patients with AAC secondary to zonular laxity who are misdiagnosed as APAC, severe complications like malignant glaucoma may occur postoperatively [9]. It is crucial to properly ascertain the condition of the zonule preoperatively because this is a determining factor pertaining to whether the surgery can be safely conducted.

Although there are studies revealing the pathogenesis of APAC and AAC owing to lens subluxation [10–14], the pathogenesis and ocular characteristics of AAC secondary to zonular laxity has not been reported yet. Kown et al. reported that less hyperopic spherical equivalent, longer axial length, shallower anterior chamber depth, and higher lens vault increased the likelihood of zonular instability among patients with a history of AAC attack [12]. But in that research, the ocular characteristics of patients with zonular laxity were not investigated separately. Moreover, ocular parameters such as anterior and posterior chamber area, the thickness of lens, the parameters of ciliary body and choroid have not been investigated yet, and the prediction of zonular laxity preoperatively remains baseless. In this study, we compared the ocular biometric parameters in patients with APAC and AAC secondary to zonular laxity, so as to clarify the ocular characteristics of patients with AAC secondary to zonular laxity, reveal the pathogenesis and set up preoperative diagnostic criteria for AAC secondary to zonular laxity. That would provide a theoretical basis for the selection of treatment schemes and reduce the risk of complications during cataract surgery.

Participants

From July 1, 2018 to April 1, 2021, 104 consecutive patients were enrolled who were diagnosed with AAC attack in one eye and underwent phacoemulsification and intraocular lens (IOL) implantation at the Department of Glaucoma, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. The study protocol was approved by the Institutional Review Board and all procedures conformed to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants in the study. The age, sex, and affected eye of each subject were recorded. All participants underwent complete ophthalmic evaluation, such as best-corrected visual acuity (BCVA) measurement before surgery, slit-lamp examination, gonioscopy examination, stereoscopic optic disc examination with a 90-diopter lens. Axial length (AL) and lens thickness (LT) were measured by IOL Master 500 (Carl Zeiss Meditec, Dublin, CA, USA), with choroidal thickness measured by optical coherence tomography (RTVue OCT, Optovue Inc, Fremont, CA, USA) and corneal endothelium cell counting measured by keratoendoscope (EM-3000, Tomey, Nagoya, Japan). IOP was measured during AAC attack (peak IOP) by Goldmann applanation tonometry. Visual field examination was performed with the Humphrey perimetry (Swedish Interactive Threshold Algorithm [SITA] Standard 30 − 2 or 24 − 2) if the BCVA was better than 20/400.

The criteria for AAC attack were as follows [15]: (1) the presence of any two of the following symptoms: ocular pain, nausea or vomiting, and an antecedent history of intermittent blurring of vision with haloes; (2) peak IOP > 40 mm Hg; (3) the presence of conjunctival injection, shallow anterior chamber, and mid-dilated fixed pupil with or without corneal epithelial edema; (4) the presence of an occluded angle in the affected eye as determined by gonioscopy. Only subjects with AAC attack in one eye for the first time were included. All the subjects underwent phacoemulsification and IOL implantation by the same ophthalmologist (JH) for the treatment of AAC. According to previous studies [4–7], eyes with the movement of the entire capsular bag during propagation of the capsular flap and anterior capsule striae during CCC intraoperatively and without lens subluxation were diagnosed as AAC secondary to zonular laxity. The video of the surgery was reviewed by another experienced ophthalmologist at the Department of Cataract in Zhongshan Ophthalmic Center who determined whether the subjects met the diagnostic criteria for zonular laxity. If a discrepancy existed between the two ophthalmologists, subjects would not be diagnosed as AAC secondary to zonular laxity and were excluded from the current research. Subjects with shallow anterior chamber and narrow angle in both eyes but without signs of zonular laxity were diagnosed as APAC.

Exclusion criteria were: (1) history of AAC attack or primary angle closure glaucoma in either eye; (2) lens subluxation detected preoperatively by ultrasound biomicroscopy scan or during surgery; (3) history of ocular surgeries or trauma; (4) AAC owing to other ocular diseases such as pseudoexfoliation syndrome, retinitis pigmentosa, Marfan syndrome, homocystinuria, Weill-Marchesani syndrome and so on; (5) inability to tolerate ultrasound biomicroscopy (UBM) examination.

Ultrasound Biomicroscopy

Ultrasound biomicroscopy (model SW-3200L; Tianjin Suowei Electronic Technology Co., Ltd., Tianjin, China) examination and measurement were performed within 1 week of AAC diagnosis by an experienced physician (HC) who was masked to the clinical data. Subjects lay in a supine position in a dimly lit room (illumination 60–70 lux, model TES-1339; TES Electrical Electronic Corp, Tianjin, China). Radial scan images at the 12, 3, 6, and 9 o’clock positions centered over the limbus and perpendicular sulcus-to-sulcus scan over the pupillary center were obtained. When performing scans, up to 100 images could be stored as cache in the machine at a speed of 5 images/s. After image capture, the best image was selected by two experienced physicians (LC and HC) who were both masked to the clinical data. The scan had to be centered on the pupil or over the limbus, be well-circumscribed, and show corneal epithelium/endothelium, anterior lens capsule, and iris pigment epithelium. Details of the UBM instruments and steps of examination were similar to those in our previous study [16].

Using the special caliper in the instrument, UBM parameters were measured as described previously [17–20]. The following parameters of five criteria were measured (Fig. 1): (1) Parameters of the anterior and posterior chamber (Fig. 1A, B): central anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber area (ACA), posterior chamber area (PCA). (2) Parameters of anterior chamber angle (Fig. 1C): angle opening distance 500 µm (AOD500), anterior chamber angle 500 µm (ACA500). (3) lens vault (LV) (Fig. 1A). (4) Parameters of iris: pupil diameter, iris thickness (IT500, IT750, and IT1000), iris curvature (IC); (5) Parameters of ciliary body (Fig. 1E and Fig. 2): trabecular meshwork-ciliary process distance (TCPD), iris-ciliary process distance (ICPD), trabecular–ciliary process angle (TCPA), anterior placement of ciliary body (APCB), maximum ciliary body thickness (CBTmax), ciliary body thickness at the point of the scleral spur (CBT0) and at the distance of 1000 µm (CBT1000) from the scleral spur. Each parameter was measured three times, with the mean values recorded. The reliabilities of UBM measurements have been reported in detail in our previous study and elsewhere [20, 21].

Statistical Analysis

Statistical analyses were performed using SPSS software version 25.0 (SPSS, Inc., Chicago, IL, USA). The means and standard deviations of the above parameters were calculated. Paired t-tests were used to detect the differences between the affected eyes with AAC and their fellow eyes. Independent t-tests were used to detect the differences in affected eyes between patients with APAC and AAC secondary to zonular laxity, and the differences in fellow eyes between the two groups. Gender and the affected eye between the two groups were compared using the chi-square test. Univariate regression was conducted to evaluate age, gender, peak IOP, AL, anterior segment parameters and the binocular difference in each group as predictors of the diagnosis of AAC secondary to zonular laxity. Parameters that were significant at a level of P < 0.05 were included in a multiple linear regression model and the regression equation was calculated. The area under the curve (AUC) was used to evaluate the diagnostic efficiency of the parameters which were significant in multiple linear regression analysis, as well as the efficiency of the regression equation. A P < 0.05 was considered statistically significant.

A total of 50 patients with AAC secondary to zonular laxity and 54 patients with APAC met the inclusion criteria were included in the current study. Demographic and biometric characteristics are summarized in Table 1. AL was shorter in both affected eyes (P = 0.006) and fellow eyes (P = 0.005) respectively in patients with APAC compared to patients with secondary AAC. There was no significant difference in demographic characteristics, vision indexes, peak IOP, choroidal thickness and corneal endothelial cell counting between the two groups (all P > 0.05).

Table 1

**Demographic and biometric characteristics of patients with APAC and AAC secondary to zonular laxity**
	APAC, n = 54		AAC secondary to zonular laxity, n = 50		P
	Affected eyes (A)	Fellow eyes (B)	Affected eyes (C)	Fellow eyes (D)	AvsB^†		CvsD^†	AvsC^‡	BvsD^‡
Sex, male/female	9/45		16/34		0.059^*
Age, y	63.24 ± 8.30		62.80 ± 7.42		0.776^‡
Affected eye, OD/OS	34/20		24/26		0.102^*
Preoperative logMAR BCVA	0.51 ± 0.28	0.20 ± 0.09	0.45 ± 0.31	0.15 ± 0.06	< 0.001	< 0.001		0.468	0.047
Peak IOP, mm Hg	47.55 ± 10.00	/	45.03 ± 9.57	/	/	/		0.464	/
MD of VF, dB	-10.34 ± 8.31	-5.89 ± 5.19	-8.30 ± 8.88	-3.26 ± 2.42	< 0.001	0.001		0.090	0.006
PSD of VF, dB	4.40 ± 2.57	3.72 ± 2.29	3.69 ± 2.58	2.74 ± 2.05	0.165	0.017		0.096	0.01
VFI, %	77.25 ± 28.71	90.39 ± 15.13	83.36 ± 28.12	96.46 ± 4.98	0.001	< 0.001		0.047	0.017
Axial length, mm	22.25 ± 0.78	22.27 ± 0.70	22.69 ± 0.67	22.72 ± 0.71	0.891	0.353		0.006	0.005
Choroidal thickness, µm	325.63 ± 96.22	315.04 ± 102.06	311.17 ± 103.64	313.38 ± 109.69	0.696	0.554		0.853	0.561
Corneal endothelial cell counting, n/mm²	2189.92 ± 840.64	2594.00 ± 391.72	2467.30 ± 490.47	2616.84 ± 359.20	0.011	0.455		0.230	0.915
Data are presented as mean ± SD. Bold values indicate statistical significance. APAC, acute primary angle closure; AAC, acute angle closure; OD, right eye; OS, left eye; BCVA, best-corrected visual acuity; IOP, intraocular pressure; MD, mean deviation; VF, visual field; PSD, pattern standard deviation; VFI, visual field index.
*, chi-square test;
^†, paired t-test;
^‡, independent t-test.

Comparison of parameters of the anterior and posterior chamber were shown in Table 2 and Fig. 3. ACD, ACA, AOD500, and ACA500 were smaller in affected eyes than in fellow eyes in both groups (all P < 0.001). In affected eyes, they were even smaller in patients with secondary AAC than patients with APAC (P < 0.001, P < 0.001, P = 0.020, P = 0.025, respectively), while in fellow eyes they were larger in patients with secondary AAC (P < 0.001, P = 0.006, P < 0.001, P < 0.001, respectively).

Table 2

Comparison of parameters of anterior and posterior chamber of patients with APAC and AAC secondary to zonular laxity
	APAC		AAC secondary to zonular laxity		P
	Affected eyes (A)	Fellow eyes (B)	Affected eyes (C)	Fellow eyes(D)	AvsB^†	CvsD^†	AvsC^‡	BvsD^‡
ACD, mm	1.73 ± 0.22	1.82 ± 0.22	1.49 ± 0.24	2.03 ± 0.32	< 0.001	< 0.001	< 0.001	< 0.001
ACW, mm	11.19 ± 1.87	11.23 ± 0.56	11.57 ± 0.72	11.36 ± 0.82	0.008	0.002	0.148	0.173
ACA, mm²	12.15 ± 1.73	12.79 ± 1.80	11.20 ± 1.39	13.67 ± 1.21	< 0.001	< 0.001	< 0.001	0.006
PCA, mm²	1.20 ± 0.35	1.05 ± 0.44	1.13 ± 0.23	1.07 ± 0.36	0.341	0.254	0.582	0.427
AOD500, mm	0.024 ± 0.041	0.072 ± 0.052	0.019 ± 0.073	0.134 ± 0.077	< 0.001	< 0.001	0.020	< 0.001
ACA500, °	2.342 ± 3.901	8.302 ± 6.211	1.262 ± 4.023	14.282 ± 6.811	< 0.001	< 0.001	0.025	< 0.001
Data are presented as mean ± SD. Bold values indicate statistical significance. APAC, acute primary angle closure; AAC, acute angle closure; ACD, central anterior chamber depth; ACW, anterior chamber width; ACA, anterior chamber area; PCA, posterior chamber area; AOD500, angle opening distance 500 µm; ACA500, anterior chamber angle 500 µm.
^†, paired t-test.
^‡, independent t-test.

Comparison of parameters of lens, iris and ciliary body were shown in Table 3 and Fig. 3. There was no significant difference in LT in affected eyes between the two groups (P > 0.05). LV was larger in affected eyes than in fellow eyes in both groups (both P < 0.05), and it was larger in affected eyes in patients with secondary AAC than in patients with APAC (P < 0.001). As shown in Table 3, IT500, IT750, and IT1000 were smaller in affected eyes in patients with secondary AAC than their fellow eyes (all P < 0.001) and affected eyes in patients with APAC (all P < 0.001). IC was larger in affected eyes in patients with secondary AAC than in patients with APAC (P = 0.006). As for parameters of the ciliary body, ICPD was smaller in affected eyes in patients with APAC than patients with secondary AAC (P = 0.003). TCPA was smaller in affected eyes in patients with APAC than their fellow eyes and affected eyes in patients with secondary AAC (P = 0.007, P = 0.005, respectively).

Table 3

Comparison of parameters of lens, iris and ciliary body of patients with APAC and AAC secondary to zonular laxity
	APAC					P
	Affected eyes (A)	Fellow eyes (B)	Affected eyes (C)	Fellow eyes(D)		AvsB^†	CvsD^†		AvsC^‡	BvsD^‡
LT, mm	5.042 ± 0.250	5.064 ± 0.231	5.113 ± 0.424		5.042 ± 0.401	0.329	0.007	0.409		0.912
LV, mm	1.089 ± 0.241	0.997 ± 0.228	1.444 ± 0.357		0.979 ± 0.267	0.003	< 0.001	< 0.001		0.507
PD, mm	4.162 ± 1.082	2.869 ± 0.771	3.957 ± 1.144		2.950 ± 1.050	< 0.001	< 0.001	0.382		0.641
IT500, mm	0.374 ± 0.089	0.383 ± 0.091	0.317 ± 0.081		0.387 ± 0.074	0.353	< 0.001	< 0.001		0.739
IT750, mm	0.403 ± 0.080	0.392 ± 0.099	0.336 ± 0.074		0.396 ± 0.075	0.617	< 0.001	< 0.001		0.799
IT1000, mm	0.449 ± 0.081	0.421 ± 0.108	0.368 ± 0.078		0.416 ± 0.084	0.346	< 0.001	< 0.001		0.993
IC, mm	0.126 ± 0.104	0.246 ± 0.091	0.185 ± 0.103		0.242 ± 0.088	< 0.001	0.01	0.006		0.815
TCPD, mm	0.487 ± 0.143	0.556 ± 0.163	0.540 ± 0.189		0.579 ± 0.133	0.024	0.124	0.157		0.200
ICPD, mm	0.122 ± 0.135	0.097 ± 0.126	0.199 ± 0.154		0.092 ± 0.116	0.207	< 0.001	0.003		0.720
TCPA, °	50.779 ± 13.134	57.173 ± 15.463	59.148 ± 14.324		59.353 ± 9.921	0.007	0.651	0.005		0.293
APCB, mm	0.545 ± 0.217	0.599 ± 0.226	0.482 ± 0.197		0.579 ± 0.200	0.024	0.124	0.157		0.200
CBT0, mm	0.930 ± 0.201	1.004 ± 0.201	1.003 ± 0.188		1.024 ± 0.140	0.039	0.204	0.144		0.506
CBT1000, mm	0.716 ± 0.174	0.722 ± 0.154	0.747 ± 0.164		0.762 ± 0.150	0.776	0.308	0.309		0.178
CBTmax, mm	1.005 ± 0.219	1.083 ± 0.141	1.018 ± 0.209		1.120 ± 0.177	0.057	0.010	0.625		0.157
Data are presented as mean ± SD. Bold values indicate statistical significance. APAC, acute primary angle closure; AAC, acute angle closure; LT, lens thickness; LV, lens vault; PD, pupil diameter; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 µm from the iris root. IC, iris curvature; TCPD, trabecular meshwork-ciliary process distance; ICPD, iris-ciliary process distance; TCPA, trabecular–ciliary process angle; APCB, anterior placement of ciliary body; CBT0, ciliary body thickness at the point of the scleral spur; CBT1000, ciliary body thickness at the distance of 1000 µm from the scleral spur; CBTmax, ciliary body thickness.
^†, paired t-test. ^‡, independent t-test.

We also compared the binocular difference of all the parameters, as shown in Table 4 and Fig. 4. Binocular difference of ACD, ACA, AOD500, ACA500, LT, LV, IT500, IT750 and IT1000 were larger in patients with secondary AAC than in patients with APAC respectively, while the binocular difference of IC was smaller (all P < 0.05).

Table 4

Comparison of the binocular difference of the parameters of patients with APAC and AAC secondary to zonular laxity
	Binocular difference		P^‡
	APAC	AAC secondary to zonular laxity	P^‡
ACD, mm	-0.091 ± 0.108	-0.542 ± 0.344	< 0.001
ACW, mm	-0.094 ± 1.881	0.170 ± 0.403	0.776
ACA, mm²	-0.643 ± 0.204	-0.882 ± 0.330	< 0.001
PCA, mm²	-0.150 ± 0.029	-0.021 ± 0.024	0.745
AOD500, mm	-0.052 ± 0.076	-0.104 ± 0.077	0.007
ACA500, °	-7.109 ± 7.215	-11.890 ± 7.724	0.012
LT, mm	-0.017 ± 0.111	0.074 ± 0.188	0.002
LV, mm	0.082 ± 0.165	0.466 ± 0.230	< 0.001
PD, mm	1.299 ± 1.035	0.979 ± 1.502	0.183
IT500, mm	-0.012 ± 0.093	-0.072 ± 0.088	0.004
IT750, mm	0.010 ± 0.093	-0.059 ± 0.084	0.001
IT1000, mm	0.027 ± 0.087	-0.048 ± 0.095	< 0.001
IC, mm	-0.131 ± 0.108	-0.052 ± 0.130	0.005
TCPD, mm	-0.071 ± 0.185	-0.042 ± 0.201	0.517
ICPD, mm	0.027 ± 0.145	0.107 ± 0.182	0.061
TCPA, °	-6.788 ± 15.774	-0.458 ± 13.201	0.068
APCB, mm	-0.054 ± 0.253	-0.093 ± 0.223	0.491
CBT0, mm	-0.071 ± 0.270	-0.024 ± 0.171	0.462
CBT1000, mm	-0.008 ± 0.233	-0.017 ± 0.152	0.857
CBTmax, mm	-0.074 ± 0.248	-0.106 ± 0.223	0.143
Data are presented as mean ± SD. Bold values indicate statistical significance. APAC, acute primary angle closure; AAC, acute angle closure; ACD, central anterior chamber depth; ACW, anterior chamber width; ACA, anterior chamber area; PCA, posterior chamber area; AOD500, angle opening distance 500 µm; ACA500, anterior chamber angle 500 µm. LT, lens thickness; LV, lens vault; PD, pupil diameter; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 µm from the iris root. IC, iris curvature; TCPD, trabecular meshwork-ciliary process distance; ICPD, iris-ciliary process distance; TCPA, trabecular–ciliary process angle; APCB, anterior placement of ciliary body; CBT0, ciliary body thickness at the point of the scleral spur; CBT1000, ciliary body thickness at the distance of 1000 µm from the scleral spur; CBTmax, ciliary body thickness.
^‡, independent t-test.

The results of regression analysis were shown in Table 5. Diagnosis of AAC secondary to zonular laxity was significantly associated with ACD, LV in affected eyes and binocular difference of ACD and LV (P = 0.003, P < 0.001, P < 0.001, P < 0.001, respectively). Among these parameters, LV in affected eyes and binocular difference of ACD and LV were significant in multiple linear regression analysis. AUC was used to evaluate the diagnostic efficiency of LV in affected eyes and binocular difference of ACD and LV, counting 0.796, 0.972 and 0.855, respectively (Fig. 5A-C). The cut-off values were 1.28, 0.23, 0.19, respectively, indicating that when LV in affected eyes exceeds 1.28 mm, or binocular difference of ACD exceeds 0.23 mm, or binocular difference of LV exceeds 0.19 mm, the diagnosis of AAC secondary to zonular laxity should be considered. The regression equation containing these three parameters was:

Table 5

Univariate and multivariate regression analyses of diagnosis of AAC secondary to zonular laxity
	Univariate		Multivariate
	OR	P	OR, (95% CI)	P
Age	0.96	0.084
Sex	1.75	0.477
Peak IOP	0.96	0.375
Axial length	1.22	0.156
ACD	0.63	0.003	0.99, (0.39–1.21)	0.421
ACA	1.33	0.363
AOD500	0.95	0.321
ACA500	0.85	0.102
LT	1.12	0.219
LV	1.89	<0.001	1.45, (1.10–2.46)	0.029
IT500	1.07	0.095
IT750	1.35	0.292
IT1000	1.22	0.899
IC	0.99	0.486
TCPD	1.64	0.358
TCPA	1.08	0.867
Binocular difference of ACD	1.68	<0.001	1.89, (1.33–4.47)	0.004
Binocular difference of AOD500	0.99	0.307
Binocular difference of ACA500	0.82	0.121
Binocular difference of LT	1.03	0.091
Binocular difference of LV	0.56	<0.001	1.38, (1.03–3.95)	0.047
Binocular difference of IC	1.03	0.176
Bold values indicate statistical significance. AAC, acute secondary angle closure; IOP, intraocular pressure; ACD, central anterior chamber depth; ACA, anterior chamber area; AOD500, angle opening distance 500 µm; ACA500, anterior chamber angle 500 µm. LT, lens thickness; LV, lens vault; IT500, IT750, IT1000, iris thickness at 500, 750, and 1000 µm from the iris root. IC, iris curvature; TCPD, trabecular meshwork-ciliary process distance; TCPA, trabecular–ciliary process angle.

ln (p/(1-p)) = -4.322 + 1.222[LV in affected eyes (mm)] + 3.657[binocular difference of LV (mm)] + 6.542[binocular difference of ACD (mm)]

In this equation, p referred to the possibility of diagnosing AAC secondary to zonular laxity. The AUC of the equation was 0.981 as shown in Fig. 5D and the accuracy of prediction of the regression equation reached 94.05%.

In the current study, we compared the ocular biometric parameters between patients with APAC and AAC secondary to zonular laxity. We found that three parameters, including LV in affected eyes, the binocular difference of ACD and the binocular difference of LV, had high efficiency in the diagnosis of AAC secondary to zonular laxity. The regression equation containing these parameters had higher diagnostic accuracy reaching 94.05%. To the best of our knowledge, this is the first study investigating the pathogenesis and preoperative diagnostic criteria of AAC secondary to zonular laxity by comparing the ocular biometric parameters in patients with APAC and AAC secondary to zonular laxity, which provides a piece of moderate-certainty evidence for developing appropriate follow-up treatment of different types of AAC.

ACD has been identified as an important clinical characteristic for distinguishing between APAC and lens-induced AAC [2]. Luo et al. and Xing et al. [2, 13] found that the anterior chamber was shallower in AAC eyes with lens subluxation than in APAC eyes (1.34 ± 0.45 mm vs 1.80 ± 0.24 mm, 1.25 ± 0.35 mm vs 1.64 ± 0.26 mm, respectively). In the current study, ACD in eyes with zonular laxity (1.49 ± 0.24 mm) was larger than that in eyes with secondary AAC in the two studies mentioned above. The inconsistency may arise from the subjects included. The two studies mentioned above included eyes with lens subluxation, which had a partial rupture in the zonule, leading to a more severe forward movement of the displaced lens. But in eyes with zonular laxity, the weak zonule may still have tension to a certain extent stopping the lens from severe forward movement, which makes it more difficult to differentiate AAC secondary to zonular laxity from APAC. Another important characteristic of patients with AAC secondary to zonular laxity was the high asymmetry in ACD between the affected eyes and the fellow eyes. The binocular difference of ACD was 0.542 ± 0.344 mm in cases with secondary AAC, significantly larger than that in patients with APAC, counting 0.091 ± 0.108 mm. Moreover, multiple linear regression analysis showed that the binocular difference of ACD had a high diagnostic ability for differentiating between AAC secondary to zonular laxity and APAC, with the AUC reaching 0.972. The cut-off value of the binocular difference of ACD was 0.23 mm, indicating that diagnosis of AAC secondary to zonular laxity should be considered when the binocular difference of ACD exceeded 0.23 mm in AAC patients. These results provided a new diagnostic basis for AAC secondary to zonular laxity. Consistent with the results of ACD, the current study also revealed that eyes with zonular laxity had narrower anterior chamber angle and smaller cross-sectional area of the anterior chamber than eyes with APAC, suggesting that a more crowded anterior segment was one of the characteristics of AAC secondary to zonular laxity.

As shown in our results, there was no significant difference in LT in affected eyes between patients with AAC secondary to zonular laxity and APAC in the current study. On the other hand, LV in eyes with lens subluxation was larger than that in eyes with APAC in the current study, which was consistent with the results of Kwon et al [12]. LV depended on the location and the thickness of lens. Since the thickness of lens was similar in affected eyes between patients with AAC secondary to zonular laxity and those with APAC, larger LV suggested a more forward-moving lens. This indicated that zonular laxity could lead to the movement of lens towards the anterior chamber and finally result in the shallow anterior chamber and angle closure, which might be the pathogenesis of AAC secondary to zonular laxity. Multiple linear regression analysis revealed that LV in affected eyes was another important factor in the diagnosis of AAC secondary to zonular laxity, with AUC reaching 0.796. The cut-off value of LV in affected eyes was 1.28 mm. In other words, when LV in eyes with AAC exceeded 1.28 mm, diagnosis of AAC secondary to zonular laxity should be considered. We also found that the binocular difference of LV was larger in patients with AAC secondary to zonular laxity than in those with APAC. The AUC of the binocular difference of LV reached 0.855, showing high diagnostic efficiency in the diagnosis of AAC secondary to zonular laxity, with the cut-off value counting 0.19 mm.

Our results revealed that three parameters, including binocular difference of ACD, LV in affected eyes and binocular difference of LV, had a high ability for differentiating between APAC and secondary AAC. Moreover, by logistic regression analysis, we figured out a regression equation: ln (p/(1-p)) = -4.322 + 1.222[LV in affected eyes (mm)] + 3.657[binocular difference of LV (mm)] + 6.542[binocular difference of ACD (mm)]. The AUC of this equation was 0.981 and the prediction accuracy reached 94.05%, meaning that using the equation including these three parameters had a higher diagnostic ability in the diagnosis of AAC secondary to zonular laxity. This could be beneficial to the differentiation of APAC and AAC secondary to zonular laxity preoperatively and conducive to the choice of treatment methods and the prediction of prognosis.

Our previous study has revealed that thickness, position, shape and dynamic change of iris played an important role in the pathogenesis of primary angle closure glaucoma (PACG) [22]. In the current study, peripheral IT was smaller in affected eyes in patients with AAC secondary to zonular laxity than in patients with APAC. In eyes with AAC secondary to zonular laxity, the iridolenticular diaphragm moves forward and generates pushing force towards the iris. The force combined with the effect of high IOP from the reverse direction makes the loose iris tissue thinner [23]. IC was larger in affected eyes in cases with AAC secondary to zonular laxity than in cases with APAC. IC could reflect the extent of iris bowing, which depended on the pressure difference between the posterior and anterior chamber [24]. Lens in eyes with zonular laxity moved more forward to the anterior chamber and the contact area between the iris and lens increased, resulting in a rise of resistance for aqueous to flow into the anterior chamber and aggravated pupillary block. This might reveal the pathogenesis of AAC secondary to zonular laxity.

Although there is various equipment for visualizing the anterior segment, UBM has been proven to be one of the most helpful methods for visualizing the posterior chamber structures, including the lens zonule and the ciliary body [25]. Therefore, we used UBM for evaluation of the integrity of zonule as well as the measurement of ciliary body parameters. In the current study, ICPD and TCPA were smaller in affected eyes in patients with APAC than patients with secondary AAC, indicating that ciliary body in eyes with zonular laxity was not as anteriorly rotated as in eyes with APAC. Therefore, the ciliary body might not be a major risk factor of AAC secondary to zonular laxity.

There were several limitations in this study. First, this is a cross-sectional study comparing AAC secondary to zonular laxity and APAC, longitudinal study is better to further reveal the dynamic pathogenesis of AAC secondary to zonular laxity. Second, although there was a significant difference in parameters of anterior chamber angle, iris and ciliary body between patients with APAC and AAC secondary to zonular laxity, only ACD and LV were included in multiple linear regression analysis and showed high diagnostic efficiency. ACD and LV could also be accurately measured by anterior segment optical coherence tomography (AS-OCT) which did not require contact with the ocular surface and was more maneuverable than UBM. Further study should be conducted to investigate the role of AS-OCT in differentiating between APAC and AAC secondary to zonular laxity. Third, the current study only included patients with AAC secondary to zonular laxity in one eye, and thus the parameters of binocular difference may not be applied to diagnosis of patients with AAC in both eyes. However, the biometric characteristics of affected eyes with AAC secondary to zonular laxity has been investigated in the current research and parameters (LV in affected eyes, for instance) could be meaningful in the diagnosis of patients with zonular laxity in both eyes.

In conclusion, binocular difference of ACD, LV in affected eyes with AAC, and binocular difference of LV had high efficiency in differentiating APAC and AAC secondary to zonular laxity. The regression equation containing these three parameters could increase the accuracy in the preoperative diagnosis of AAC secondary to zonular laxity.

Conflict of Interest:

The authors declare no competing financial interests.

Acknowledgements

Fundings: Supported by the National Natural Science Foundation of China (82271081), the Natural Science Foundation of Guangdong Province in China (2021A1515012142, 2022A1515010302), and the Research Grant from Guangzhou Municipal Science and Technology Bureau in China (202201020268).

Financial Disclosures: No financial disclosures.

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Ocular Biometric Characteristics in Preoperative Diagnosis of Acute Angle Closure Secondary to Zonular Laxity

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